Sethy V H, Ellerbrock B R, Fici G J, Wu H
Pharmacia & Upjohn Inc., Kalamazoo, MI 49001, USA.
Brain Res. 1996 Sep 9;733(1):41-5. doi: 10.1016/0006-8993(96)00531-8.
The D1 and D2 dopamine receptor agonist properties of 7-hydroxy-2-(N,N-di-n-propylamino) tetraline (7-OH-DPAT) was determined by investigating the effect of this compound on rat striatal acetylcholine (ACh) concentration and increase in cAMP formation in primary cerebellar granule cell cultures. 7-OH-DPAT at low doses (0.01 to 0.1 mumol/ kg) had no significant effect, and at high doses (0.3 to 30 mumol/kg) significantly (P < 0.01) increased striatal ACh levels. Likewise, quinpirole was found to significantly elevate ACh content. Pretreatment with haloperidol, a non-selective antagonist of the D2 family of receptors, significantly (P < 0.01) blocked 7-OH-DPAT- and quinpirole-induced increases in ACh. U-99194A, a D3 selective dopamine antagonist, had no significant effect on 7-OH-DPAT-induced increases in striatal ACh. However, raclopride, a D2 selective dopamine antagonist, completely blocked 7-OH-DPAT-induced elevations in ACh. 7-OH-DPAT in the mumolar range increased cAMP formation in granule cell cultures, and this effect was antagonized by SCH 23390, a D1 selective dopamine antagonist. The neurochemical study indicates that, at high doses, 7-OH-DPAT has both D1 and D2 agonist activities.
通过研究7-羟基-2-（N，N-二正丙基氨基）四氢萘（7-OH-DPAT）对大鼠纹状体乙酰胆碱（ACh）浓度的影响以及对原代小脑颗粒细胞培养物中cAMP生成增加的影响，来确定其多巴胺D1和D2受体激动剂特性。低剂量（0.01至0.1μmol/kg）的7-OH-DPAT无显著影响，高剂量（0.3至30μmol/kg）则显著（P<0.01）提高纹状体ACh水平。同样，喹吡罗也被发现可显著提高ACh含量。用氟哌啶醇（一种D2家族受体的非选择性拮抗剂）预处理可显著（P<0.01）阻断7-OH-DPAT和喹吡罗诱导的ACh增加。U-99194A（一种D3选择性多巴胺拮抗剂）对7-OH-DPAT诱导的纹状体ACh增加无显著影响。然而，雷氯必利（一种D2选择性多巴胺拮抗剂）完全阻断了7-OH-DPAT诱导的ACh升高。毫摩尔范围内的7-OH-DPAT增加了颗粒细胞培养物中cAMP的生成，且这种作用被D1选择性多巴胺拮抗剂SCH 23390所拮抗。神经化学研究表明，高剂量时，7-OH-DPAT具有D1和D2激动剂活性。
